Cardiovascular risk factors as determinants of retinal and skin microvascular function: The Maastricht Study

Abstract

ObjectiveMicrovascular dysfunction is an important underlying mechanism of microvascular diseases. Determinants (age, sex, hypertension, dyslipidemia, hyperglycemia, obesity, and smoking) of macrovascular diseases affect large-artery endothelial function. These risk factors also associate with microvascular diseases. We hypothesized that they are also determinants of microvascular (endothelial) function.MethodsIn The Maastricht Study, a type 2 diabetes-enriched population-based cohort study (n = 1991, 51% men, aged 59.7±8.2 years), we determined microvascular function as flicker light-induced retinal arteriolar %-dilation and heat-induced skin %-hyperemia. Multiple linear regression analyses were used to assess the associations of cardiovascular risk factors (age, sex, waist circumference, total-to-high-density lipoprotein (HDL) cholesterol ratio, fasting plasma glucose (FPG), 24-h systolic blood pressure, and cigarette smoking) with retinal and skin microvascular function.ResultsIn multivariate analyses, age and FPG were inversely associated with retinal and skin microvascular function (regression coefficients per standard deviation (SD) were -0.11SD (95%CI: -0.15;-0.06) and -0.12SD (-0.17;-0.07) for retinal arteriolar %-dilation and -0.10SD (-0.16;-0.05) and -0.11SD (-0.17;-0.06) for skin %-hyperemia, respectively. Men and current smokers had -0.43SD (-0.58;-0.27) and -0.32SD (-0.49;-0.15) lower skin %-hyperemia, respectively. 24-h systolic blood pressure, waist circumference, and total-to-HDL cholesterol ratio were not statistically significantly associated with these microvascular functions.ConclusionsAssociations between cardiovascular risk factors and retinal and skin microvascular function show a pattern that is partly similar to the associations between cardiovascular risk factors and macrovascular function. Impairment of microvascular function may constitute a pathway through which an adverse cardiovascular risk factor pattern may increase risk of diseases that are partly or wholly of microvascular origin.

Reconstructing the blood metabolome and genotype using long-range chromatin interactions

“…The tissue SNP-gene mappings identified in this study are consistent with known tissue-metabolite relationships. For example, previous studies support our observation of cholesterol-associated regulatory interactions in the basal ganglia [ 44 , 45 ], skeletal muscle [ 46 , 47 ], and skin [ 48 , 49 ]. Similarly, our observation of disproportionately high metabolism-associated eQTL interactions per RNA-Seq sample in the cerebellum and testis agrees with known metabolic dysfunction in these tissues ( e.g.…”

Cardiometabolic risk factors as determinants of peripheral nerve function: the Maastricht Study

“…A complex interplay between several mechanisms including hyperglycaemia, lipotoxicity, oxidative stress and inflammation is thought to play a central role in the pathogenesis of (diabetic) neuropathy [38]. We recently reported that microvascular function was diminished not only in people with type 2 diabetes, but also with prediabetes [39]; age, smoking and prior exposure to hypertension and dyslipidaemia, and in particular higher levels of glucose (also in the normal range), were all associated with microvascular function [40]. Observations in the current study are in line with these results, suggesting similar risk factors for generalised microvascular damage and early-stage nerve damage.…”

Microvascular Phenotyping in the Maastricht Study: Design and Main Findings, 2010–2018

“…Evaluating microvascular responses in skin and retina, we observed that older age and higher plasma glucose level were associated with both lower heat-induced skin hyperemia and lower flicker light-induced retinal arteriolar dilation ( 45 , 46 ). In addition, lower heat-induced skin hyperemia was found in men and in current smokers ( 45 ). Interestingly, we did not find any association of 24-hour systolic blood pressure with microvascular responses in skin or retina.…”

“…Interestingly, we did not find any association of 24-hour systolic blood pressure with microvascular responses in skin or retina. Instead, higher 24-hour pulse pressure was associated with lower heat-induced skin hyperemia, and higher 24-hour diastolic blood pressure was associated with increased flicker light-induced retinal arteriolar dilation ( 45 ). Higher plasma glucose level was associated with the presence of brain lacunar infarcts and larger volumes of WMHs, including deep cortical and periventricular WMHs, but not with the presence of cerebral microbleeds ( 47 ).…”